1. Field of the Invention
This invention is directed to an improved process for the preparation of nitrate stabilized 3-isothiazolone compounds substantially free of nitrosamine.
2. Description of the Prior Art
3-Isothiazolones have generated high commercial interest as microbicides to prevent spoilage of certain aqueous and non-aqueous products caused by microorganisms. Isothiazolones are highly effective microbicides (as used herein, "microbicides" includes bactericides, fungicides and algicides and microbicidal activity is intended to include both the elimination of and the inhibition or prevention of growth of microbial organisms such as bacteria, fungi and algae); by suitable choice of functional groups, they are useful in a broad range of applications. These compounds may be represented by the following general formula: ##STR2## wherein R and R.sup.1 are independently selected from hydrogen, halogen or a (C.sub.1 -C.sub.4) alkyl group; Y is hydrogen, a (C.sub.1 -C.sub.18) alkyl group, an unsubstituted or halo-substituted alkenyl or alkynyl of 2 to 8 carbon atoms, a cycloalkyl or substituted cycloalkyl of 3 to 12 carbon atoms, an aralkyl or halo-, (C.sub.1 -C.sub.4) alkyl-, or (C.sub.1 -C.sub.4) alkoxy-substituted aralkyl of up to 10 carbon atoms, or an aryl or halo-, (C.sub.1 -C.sub.4) alkyl-, (C.sub.1 -C.sub.4) alkoxy-substituted aryl group of up to 10 carbon atoms.
Unfortunately, solutions of the 3-isothiazolones, especially aqueous solutions or solutions in polar organic solvents such as alcohols containing trace to significant amounts of water, are unstable, leading to reduced biological effectiveness.
This is especially true of the 5-halogen containing 3-isothiazolones, where Y above is a C.sub.1 -C.sub.8 alkyl, an aralkyl of up to 10 carbon atoms or a cycloaliphatic radical. The instability results from an opening of the isothiazolone ring to form linear compounds which do not have the same biological properties as the ring compounds. U.S. Pat. Nos. 3,870,795 and 4,067,878 teach that in order to inhibit ring cleavage, nitrate salts, for example, those of metals such as barium, cadmium, calcium, chromium, cobalt, copper, iron, lead, lithium, magnesium, manganese, nickel, silver, sodium, strontium, tin and zinc, can be added to isothiazolone solutions. These patents also teach that other common metal salts, including chlorates and perchlorates, are ineffective in stabilizing solutions of isothiazolones. Thus it is commercially desirable today to formulate many of the 5-hologenated 3-isothiazolone biocides either alone or in combination with other 3-isothiazolone biocides in solutions containing water or organic solvent or mixtures thereof together with nitrate stabilizers to prevent decomposition of the 3-isothiazolone.
One of the existing commercial processes used for manufacturing the 3-isothiazolones includes amidation of a disulfide ester followed by the halogen induced cyclization of the amide: